Baculovirus infects insects and is non-pathogenic to humans, but can transduce a broad range of mammalian and avian cells. Thanks to the biosatety, large cloning capacity, low cytotoxicity and non-replication nature in the transduced cells as well as the ease of manipulation and production, baculovirus has gained explosive popularity as a gene delivery vector for a wide variety of applications such as antiviral therapy, cancer therapy, regenerative medicine and vaccine.
U.S. Pat. No. 7,527,967 discloses a recombinant baculovirus that displays a fusion heterologous polypeptide on the surface of the baculovirus for use in generating an antibody or an immune response against a heterologus protein or virus in a subject in need thereof. The fusion heterologous polypeptides therein is made by fusing a heterologus antigen with the carboxyl terminal amino acids from 227 to 529 of baculovirus GP64 protein (FIG. 2C). The construct therein contains a substantial portion of the extracellular domain of GP64 including B12D5 binding site. When it is used in immunization, the extracellular domain of GP64 may elicit an immune response and produce unintended antibodies such as useless anti-GP64 B12D5 antibody (Zhou et al. Virology 2006; 352(2):427-437). GP64 B12D5 antibody is a neutralization antibody against baculovirus itself instead of a foreign antigen of interest. In addition, baculovirus is slightly immunogenic to porcine.
Taiwanese Patent No. 1368656 discloses a method of using the signal peptide, transmembrane domain and the cytoplasmic transduction domain from GP64 to present an antigen. The construct therein contains only the transmembrane domain and cytoplasmic trunsduction domain without the extracellular domain of GP64 (FIG. 2D). It has less expression of foreign antigen and is sensitive to inactivation reagents (Premanand et al. PLoS ONE 2013; 8(2): e55536).
Therefore, a heretofore unaddressed need exists in the art to address the aforementioned deficiencies and inadequacies, especially in connection with a baculovirus vector that is insensitive to inactivation reagent and has improved immunogenicity.